rs201536644
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006031.6(PCNT):c.5705G>A(p.Arg1902His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,604,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1902C) has been classified as Uncertain significance.
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.5705G>A | p.Arg1902His | missense_variant | 28/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.5351G>A | p.Arg1784His | missense_variant | 28/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.5705G>A | p.Arg1902His | missense_variant | 28/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000132 AC: 30AN: 226756Hom.: 0 AF XY: 0.000119 AC XY: 15AN XY: 125944
GnomAD4 exome AF: 0.000282 AC: 409AN: 1452494Hom.: 0 Cov.: 34 AF XY: 0.000246 AC XY: 178AN XY: 722642
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 12, 2014 | - - |
PCNT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 07, 2024 | The PCNT c.5705G>A variant is predicted to result in the amino acid substitution p.Arg1902His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1902 of the PCNT protein (p.Arg1902His). This variant is present in population databases (rs201536644, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 211866). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at